Expression and cellular localization of low-density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor in human glioblastoma in vivo.

Low-density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP) has been proposed to mediate the cellular uptake and clearance of inactivated protease-inhibitor complexes in regulating proteinase activity at the cell surface, which is necessary for cellular migration and invasive processes. In this study, we investigated the presence of both LRP and urokinase-type plasminogen activator receptor (uPAR) in glioblastoma by reverse transcriptase-polymerase chain reaction (RT-PCR), and the cellular localization of LRP in glioblastoma tissues by immunohistochemical analysis. LRP mRNA was frequently expressed in glioblastomas and anaplastic astrocytomas compared with low-grade astrocytomas by RT-PCR analysis, and was well correlated with uPAR expression. The immunohistochemistry of LRP on sequential frozen sections showed that neoplastic glial cells and endothelial cells of glioblastomas exhibited intense LRP immunoreactivity, whereas LRP was almost undetectable in low-grade astrocytomas or in normal glial cells and endothelial cells of normal brain tissue. Glioblastomas from 11 patients in which the expression of LRP mRNA was observed by PCR displayed strong to moderate LRP immunoreactivity, with predominantly diffuse cytoplasmic and cell-surface localization. In normal brain tissues, LRP immunoreactivity was identified in the pyramidal neurons of the cerebral cortex. These results indicate that LRP is present both in the cellular cytoplasm and on the cell surface of glioblastomas with an increased expression of uPAR. Altered LRP expression might contribute to the stimulation of cell-surface proteolytic activity that in turn facilitates the invasiveness of glioblastoma in vivo.